An immunoglobulin contains in general two light polypeptide chains and two heavy polypeptide chains. Each of the heavy and light polypeptide chains comprises a variable region (generally the amino terminal portion of the polypeptide chain) which contains a binding domain that is able to interact with an antigen. Each of the heavy and light polypeptide chains also comprises a constant region (generally the carboxyl terminal portion). The constant region of the heavy chain mediates the binding of the immunoglobulin e.g. to cells bearing an Fc gamma receptor (FcγR), such as phagocytic cells, or to cells bearing the neonatal Fc-receptor (FcRn) also known as Brambell receptor, and also mediates the binding to some factors including factors of the classical complement system such as component (C1q).
Hulett and Hogarth (Hulett, M. D. and Hogarth, P. M., Adv. Immunol. 57 (1994) 1-127) reported that the extracellular receptors for the Fc part of immunoglobulins of class G are a family of transmembrane glycoproteins comprising three different receptor types having different binding specificity: FcγRI, FcγRII, and FcγRIII. Receptors of type I interact with non-complexed IgG, whereas receptors of type II and III interact preferably with complexed IgG.
Certain immunoglobulin-based cytokine fusion proteins are commercially available (e.g. from Biomol). FC-region fusions are reported generally in “Therapeutic monoclonal antibodies—from bench to clinic” (Wiley, Edited by Zhiqiang An, 2009).
In WO 01/03737 immunoglobulin fusion proteins are reported. Improved circulating half-life and efficacy of an antibody-interleukin 2 immunocytokine based on reduced intracellular proteolysis is reported by Gillies, S. D., et al. (Clin. Cancer Res. 8 (2002) 210-216). Dumont, J. A., et al. (Biodrugs 20 (2006) 151-160) report monomeric Fc fusions. High level expression and secretion of Fc-X fusion proteins in mammalian cells is reported by Lo, K-M., et al. (Prot. Eng. 11 (1998) 495-500). In WO 00/40615 the expression and export of anti-obesity proteins as Fc fusion proteins is reported.